Chlorhexidine Mouthwash and Oral Nitrate in Adults With Pulmonary Hypertension

NCT03787082 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY191201045P01HL103455
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-center study to examine distinguishing features of the structure and function of the oral and gut microbiome in volunteers with PH in the breakdown of oral nitrate and effect on hemodynamics.

Conditions

Pulmonary Hypertension; Heart Failure With Normal Ejection Fraction; Pulmonary Heart Disease and Diseases of Pulmonary Circulation

Outcome Measures

Primary Outcomes (6)

• Change in Plasma Nitrate

  At baseline and 2 hours post drug administration

• Change in Urine Nitrate

  At baseline and 2 hours post drug administration

• Change in Plasma Nitrate

  At baseline and 6 hours post drug administration

• Change in Urine Nitrate

  At baseline and 6 hours post drug administration

• Change in Plasma Nitrate

  At 2 hours post drug administration and 6 hours post drug administration

• Change in Urine Nitrate

  At 2 hours post drug administration and 6 hours post drug administration

Secondary Outcomes (1)

• Change in Pulmonary Vascular Resistance (PVR)

  At baseline and 2 hours post drug administration

Study Arms (2)

Chlorhexidine Gluconate Mouthwash

EXPERIMENTAL

rinse with chlorhexidine gluconate 0.12% (15mL) mouthwash before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral

Drug: Nitrates; Drug: Chlorhexidine Gluconate Mouthwash

Placebo Mouthwash

PLACEBO COMPARATOR

rinse with placebo mouthwash (15mL) before administration of 14N Sodium Nitrate 1,000 mg/11.18 mmol, oral

Drug: Nitrates; Drug: Placebo Mouthwash

Interventions

Nitrates DRUG

1,000 mg/11.18 mmol, oral

Also known as: 14N Sodium Nitrate

Chlorhexidine Gluconate Mouthwash; Placebo Mouthwash

Chlorhexidine Gluconate Mouthwash DRUG

chlorhexidine gluconate 0.12% (15mL) mouth rinse for 1 minute

Also known as: Chlorhexidine mouthwash

Chlorhexidine Gluconate Mouthwash

Placebo Mouthwash DRUG

sterile water (15mL) mouth rinse for 1 minute

Also known as: Sterile Water

Placebo Mouthwash

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 years of age or older
• Undergoing clinical right heart catheterization or had a RHC in past 5 years if in PH group
• Pulmonary Hypertension: hemodynamically defined by a mean PAP ≥ 25 mm Hg and have a PVR \> 3 Woods units and normal cardiac index (\>2.0 L/min/m2)
• Healthy Control group: no history of or active cardiac or pulmonary disease
• Ability to provide written informed consent

You may not qualify if:

• Use of systemic antibiotics and/or chlorhexidine mouthwash within the previous three months
• Use of immune suppression (chemotherapy, oral prednisone greater than 20mg per day, etc) with in the previous three months
• Use of phosphodiesterase-5 inhibitors (tadalafil, sildenafil, etc) within 7 days before study drug administration
• Current pregnancy or lactation
• Uncontrolled systemic hypertension based on repeated measurement of sitting systolic blood pressure \>185 mm Hg or sitting diastolic blood pressure \>110 mm Hg
• Has chronic renal insufficiency as defined by serum creatinine \>3 mg/dL in the last 6 months or requiring dialytic support as reported in the medical record
• Known history of left ventricular ejection fraction \< 40% by multiple gated acquisition scan (MUGA), angiography, or echocardiography
• History of atrial septostomy
• Repaired or unrepaired congenital heart disease
• Pericardial constriction
• Restrictive or constrictive cardiomyopathy
• Symptomatic coronary disease with demonstrable ischemia
• Addition or change in dosing of hormonal contraception medications (OCP, IUD, Depo-Provera) in the past 4 weeks.
• Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study or would prevent completion of the study
• Active participation in other research studies with investigational drugs

Sponsors & Collaborators

• Gladwin, Mark, MD: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Pittsburgh: collaborator

Study Sites (1)

Cathy Kessinger

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Heart Disease

Interventions

Nitrates

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals

Study Officials

• Alison Morris, MD, MS

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants will receive open label nitrate and be randomly assigned to either chlorhexidine mouthwash or placebo mouthwash. The participant and investigator will be blinded to which mouthwash the participant is randomized.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 24, 2018
• First Posted: December 26, 2018
• Study Start: December 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: July 7, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be made following publication.
• Access Criteria: Data will be available publicly.

Locations

US (1)